Opportunity for a Cooperative Research and Development Agreement (CRADA) for Research and Development of Vigabatrin as a Potential Pharmacotherapy for the Treatment of Cocaine and Methamphetamine Dependence, 29330-29332 [05-10066]
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Federal Register / Vol. 70, No. 97 / Friday, May 20, 2005 / Notices
food effect. In its February 15, 1994,
letter accompanying NDA 50–711,
Pfizer explained that the tablets are
bioequivalent to the capsule formulation
and ‘‘* * * unlike the capsule, can be
taken without regard to meals.’’ After
NDA 50–711 was approved, Pfizer
decided not to market the capsule
formulation and ZITHROMAX
(azithromycin) 250-mg oral capsules
were moved from the prescription drug
product list to the ‘‘Discontinued Drug
Product List’’ section of the Orange
Book. The ‘‘Discontinued Drug Product
List’’ delineates, among other items,
drug products that have been
discontinued from marketing for reasons
other than safety or effectiveness.
In a citizen petition submitted under
21 CFR 10.30 dated May 4, 2004 (Docket
No. 2004P–0220), as amended by a letter
dated May 17, 2004, Wapner, Newman,
Wigrizer & Brecher requested that FDA
determine whether ZITHROMAX
(azithromycin) 250-mg oral capsules
were withdrawn from sale for reasons of
safety or effectiveness. The agency has
determined that ZITHROMAX
(azithromycin) 250-mg oral capsules
were not withdrawn from sale for
reasons of safety or effectiveness. The
petitioners identified no data or other
information suggesting that
ZITHROMAX (azithromycin) 250-mg
oral capsules were withdrawn from sale
as a result of safety or effectiveness
concerns. FDA has independently
evaluated relevant literature and data
and has found no information that
would indicate this product was
withdrawn for reasons of safety or
effectiveness.
After considering the citizen petition
and reviewing agency records, FDA
determines that, for the reasons outlined
in this document, ZITHROMAX
(azithromycin) 250-mg oral capsules,
approved under NDA 50–670, were not
withdrawn from sale for reasons of
safety or effectiveness. Accordingly, the
agency will continue to list
ZITHROMAX (azithromycin) 250-mg
oral capsules in the ‘‘Discontinued Drug
Product List’’ section of the Orange
Book. As a result, ANDAs that refer to
ZITHROMAX (azithromycin) 250-mg
oral capsules may be approved by the
agency.
Dated: May 12, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05–10032 Filed 5–19–05; 8:45 am]
BILLING CODE 4160–01–S
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Health Resources and Services
Administration
National Advisory Committee on Rural
Health and Human Services; Notice of
Meeting
In accordance with section 10(a)(2) of
the Federal Advisory Committee Act
(Pub. L. 92–463), notice is hereby given
that the following committee will
convene its fiftieth meeting:
Name: National Advisory Committee on
Rural Health and Human Services.
Dates and Times: June 12, 2005, 1:30 p.m.–
5:15 p.m., June 13, 2005, 8:45 a.m.–5 p.m.,
June 14, 2005, 9 a.m.–10:45 a.m.
Place: Carnegie Hotel, 1216 W State of
Franklin Road, Johnson City, TN 37604,
Phone: 423–979–6400, Fax: 423–979–6424.
Status: The meeting will be open to the
public.
Purpose: The National Advisory
Committee on Rural Health and Human
Services provides advice and
recommendations to the Secretary with
respect to the delivery, research,
development, and administration of health
and human services in rural areas.
Agenda: Sunday afternoon, June 12, at 1:30
p.m., the Chairperson, the Honorable David
Beasley, will open the meeting and welcome
the Committee. There will be a brief
discussion of Committee business and
updates by Federal staff. The first session
will open with an overview of East
Tennessee by Dr. Paul Stanton, President of
East Tennessee State University. The
remainder of the day’s meeting will be
devoted to panel discussions on the three
topics for the 2006 workplan: Pharmacy
Access, Health Information Technology
(HIT), and Elderly Caregiver Support. The
Sunday meeting will close at 5:15 p.m.
Monday morning, June 13, at 8:45 a.m., the
Committee will break into Subcommittees
and conduct site visits to local health and
human services facilities. Transportation to
these sites will not be provided to the general
public. The Pharmacy Access Subcommittee
will visit Wilson Pharmacy in Johnson City;
the HIT Subcommittee will visit Central
Appalachian Health Information Partnership
in Mountain City; and the Elderly Caregiver
Support Subcommittee will visit the
Mountain Empire Older Citizens Area
Agency on Aging in Big Stone Gap. The
Subcommittees will reconvene at 1:45 p.m. at
the Carnegie Hotel to continue discussions
on the workplan. The Committee of the
whole will reconvene at 4:30 p.m. for a brief
discussion of the workplan. The Monday
meeting will close at 5 p.m.
The final session will be convened
Tuesday morning, June 14, at 9 a.m. The
Committee will review the discussion of the
2006 Workplan and have updates on the
Subcommittees site visits. The meeting will
conclude with a discussion of the September
meeting. The meeting will be adjourned at
10:45 a.m.
For Further Information Contact: Anyone
requiring information regarding the
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Committee should contact Tom Morris,
M.P.A., Executive Secretary, National
Advisory Committee on Rural Health and
Human Services, Health Resources and
Services Administration, Parklawn Building,
Room 9A–55, 5600 Fishers Lane, Rockville,
MD 20857, telephone (301) 443–0835, Fax
(301) 443–2803.
Persons interested in attending any portion
of the meeting should contact Michele PrayGibson, Office of Rural Health Policy
(ORHP), telephone (301) 443–0835. The
Committee meeting agenda will be posted on
ORHP’s Web site https://
www.ruralhealth.hrsa.gov.
Dated: May 13, 2005.
Tina M. Cheatham,
Director, Division of Policy Review and
Coordination.
[FR Doc. 05–10098 Filed 5–19–05; 8:45 am]
BILLING CODE 4165–15–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Opportunity for a Cooperative
Research and Development Agreement
(CRADA) for Research and
Development of Vigabatrin as a
Potential Pharmacotherapy for the
Treatment of Cocaine and
Methamphetamine Dependence
National Institutes of Health,
PHS, DHHS.
AGENCY:
ACTION:
Notice.
SUMMARY: The National Institute on
Drug Abuse, a component of the
National Institutes of Health,
Department of Health and Human
Services (DHHS) seeks an agreement
with a pharmaceutical or biotechnology
company to test the hypotheses that
vigabatrin may be a safe and effective
medication for the treatment of cocaine
and methamphetamine dependence.
A body of literature relevant to
preclinical studies of vigabatrin as a
potential treatment agent for various
types of substance dependence
(including cocaine and
methamphetamine) and a more limited
body of literature concerning clinical
results exists. As there are currently no
medications approved by the U. S. Food
and Drug Administration (FDA) for the
treatment of cocaine and/or
methamphetamine dependence, and
cocaine and methamphetamine
dependence have substantial negative
public health impacts, the National
Institute on Drug Abuse is interested in
evaluating the safety and efficacy of
vigabatrin for the treatment of cocaine
and methamphetamine dependence.
E:\FR\FM\20MYN1.SGM
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Federal Register / Vol. 70, No. 97 / Friday, May 20, 2005 / Notices
Rationale for Studying Vigabatrin in
Stimulant(s) Dependence
The dependence-producing properties
of stimulants have been associated with
their pharmacological actions on the
mesolimbic dopamine reward pathways
in the central nervous system (CNS).
Gamma-amino butyric acid (GABA)
inhibits striatal dopamine release, and
attenuates cocaine-induced increases in
extracellular dopamine in the striatum
and nucleus accumbens (Molina et. al.,
1999). Selective increases in GABAergic
tone attenuate cocaine-induced
dopamine release without the apparent
side effects typically associated with
GABA agonists. Therefore, targeting
brain GABAergic systems is a
potentially effective pharmacologic
treatment strategy for cocaine and
methamphetamine dependence (Molina
et. al., 1999). Data from proof of concept
clinical trials of similar GABAergic
medications e.g. topiramate, baclofen,
and tiagabine show efficacy in reducing
cocaine use or in preventing relapse to
use. These data suggest that vigabatrin,
which possesses more potent
GABAergic action, may be more
efficacious than these medications.
Preclinical studies in animal models
have confirmed that dosing with
vigabatrin can block the manifestations
of consumption of cocaine typically
seen in these models (Stromberg et. al.,
2001), without impairing the usual
dopamine mechanisms necessary to
maintain a stable equilibrium. In rodent
models, vigabatrin has been shown to
reduce self-administration of cocaine
and alcohol (Stromberg et. al., 2001;
Kushner et al., 1999), and to block
conditioned place preference induced
by cocaine (Dewey et. al, 1998), nicotine
(Dewey et. al., 1999), and heroin (Paul,
et. al., 2001). Further, vigabatrin can
reduce the increases in nucleus
accumbens dopamine induced by
cocaine (Schiffer et. al., 2003), as well
as methamphetamine, heroin, and
ethanol (Gerasimov et. al., 1999).
Vigabatrin (GVG) is an irreversible
gamma-amino butyric acid (GABA)
transaminase inhibitor that produces a
two to three fold rise in brain GABA
concentrations (Guberman et. al., 2000).
Following oral administration,
vigabatrin readily crosses the bloodbrain barrier and is active within the
central nervous system. It has been
shown to be effective, both as an addon agent and in monotherapy in
resistant and newly-diagnosed epilepsy
(Guberman et. al., 2000) and as first line
monotherapy in the treatment of
infantile spasms (West syndrome)
(Hancock et. al., 1999). After oral
dosing, vigabatrin is well absorbed
VerDate jul<14>2003
20:07 May 19, 2005
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(bioavailability c. 75%) and widely
distributed. The drug is eliminated
primarily by the renal route and is not
significantly bound to plasma proteins.
The elimination half-life is
approximately 5–9 hours in healthy
subjects and may be prolonged in
elderly patients or those with impaired
renal function (Rey et. al., 1992). The
usual adult dose of vigabatrin for
epilepsy is 1–3 g/day. There is no
evidence that plasma concentrations of
vigabatrin correlate closely with
therapeutic effects (Brodie et. al., 2003).
There are anecdotal reports that
dosing with vigabatrin prevents the
‘‘high’’ associated with cocaine intake in
humans dependent on cocaine and can,
therefore, result in decreased cocaine
consumption. Two open label pilot
studies suggest a therapeutic effect in
most patients recruited in abstaining
from cocaine or methamphetamine
(Brodie et. al., 2005) use (Brodie et. al.,
2003; Brodie et. al., 2005).
Therefore, it may be predicted that
dosing with vigabatrin in a cocaine
dependent population might prevent the
cocaine ‘‘high’’ and the subsequent
‘‘craving’’, and possibly reduce the
perceived need for repeated use, and
often higher, drug doses (Dewey et. al.,
1999).
As an initial step in the clinical
development of vigabatrin for
stimulants dependence, it is important
to assess the potential efficacy and
safety of this compound in cocaine and
methamphetamine dependent subjects.
References
Brodie JD, Figueroa E, Dewey SL (2003).
Treating cocaine addiction: From
preclinical to clinical experience with
gamma-vinyl GABA. Synapse 50: 261–265.
Brodie JD, Figueroa E, Lasha EM, Dewey SL
(2005). Safety and efficacy of gamma-vinyl
GABA (GVG) for the treatment of
methamphetamine and cocaine addiction.
Synapse 55(2): 122–125.
Dewey SL, Brodie JD, Gerasimov M, Horan B,
Gardner EL, Ashby CR (1999). A
pharmacological strategy for the treatment
of nicotine addiction. Synapse 31: 76–86.
Dewey SL, Morgan SE, Ashby CR, Horan B,
Gardner EL, Brodie JD (1998). A novel
strategy for the treatment of cocaine
addiction. Synapse 30: 119–129.
Gerasimov MR, Ashby CR, Gardner EL, Mills
MJ, Brodie JD, Dewey SL (1999). GammaVinyl GABA inhibits methamphetamine,
heroin, or ethanol-induced increases in
nucleus accumbens dopamine. Synapse 34:
11–19.
Gillis MC (2005). CPS: Compendium of
Pharmaceutical and Specialties (CPS). 37th
Edition, Canadian Pharmaceutical
Association, Ottawa, pp: 1513–1515.
Guberman A, Bruni J & The Canadian
Vigabatrin Study Group (2000). Long-term
open multicentre, add-on trial of vigabatrin
PO 00000
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29331
in adult resistant partial epilepsy. Seizure
9:112–118.
Hancock E, Osborne JP (1999). Vigabatrin in
the treatment of infantile spasms in
tuberous sclerosis. J Child Neurol 14:71–
74.
Kushner SA, Dewey SL, Kornetsky C (1999).
The irreversible gamma-amino butyric acid
(GABA) transaminase inhibitor gamma
vinyl-GABA blocks cocaine selfadministration in rats. J.Pharmacol
ExpTher 290(2): 797–802.
Molina PE, Ahmed N, Ajmal M, Dewey S,
Volkow N, Fowler J, Abumrad N (1999).
Co-administration of Gamma-Vinyl GABA
and Cocaine: Preclinical Assessment of
Safety. Life Sciences 11:1175–1182.
Rey E, Pons G, Olive G (1992). Vigabatrin.
Clinical pharmacokinetics. Clin
Pharmacokinet 23:267–278.
Schiffer WK, Martsteller D, Dewey SL (2003).
Sub-chronic low dose gamma vinyl GABA
(vigabatrin) inhibits cocaine-induced
increases in nucleus accumbens dopamine.
Psychopharmacology 168: 339–343.
Stromberg MF, Mackler SA, Volpicelli JR,
O’Brien CP, Dewey SL (2001). The effect of
gamma-vinyl-GABA on the consumption of
concurrently available oral cocaine and
ethanol in the rat. Pharmacol Biochem
Behav 68:291–299.
NIDA will consider all proposals
received within 45 days of the date of
publication of this notice. This notice is
active until July 5, 2005.
ADDRESSES: Proposals and questions
about this opportunity may be
addressed to Frank Vocci, Ph.D.,
Division of Pharmacotherapy and
Medical Consequences of Drug Abuse,
National Institute on Drug Abuse, 6001
Executive Blvd., MSC 9551, Bethesda,
Maryland 20892–9551. For overnight
mail service, 6001 Executive Blvd.,
Room 4123, Rockville, Maryland 20852.
Tel: (301) 443–2711, Fax: (301) 443–
2599.
SUPPLEMENTARY INFORMATION: NIDA will
consider proposals from all qualified
entities and will, subject to negotiation
of the details of a mutually agreed upon
Research Plan, provide the CRADA
Collaborator access to its comprehensive
preclinical and clinical trials resources
with the understanding that the CRADA
Collaborator will be able to utilize data
derived from the CRADA to pursue
regulatory filings in the U.S. and abroad.
NIDA’s Medications Development
Program possesses the capacity to
perform chemical synthesis, dosage
form development, pharmacokinetics,
pharmacodynamics, toxicology,
regulatory management, and clinical
testing (Phase I through Phase III)
meeting FDA requirements for Good
Manufacturing, Good Laboratory
Procedures, and Good Clinical Practices
standards. NIDA may apply these
capacities in the assessment of
vigabatrin, as may be warranted based
DATES:
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Federal Register / Vol. 70, No. 97 / Friday, May 20, 2005 / Notices
on NIDA’s evaluation of the
information, capacities, and plans
provided by potential Collaborator(s).
NIDA follows stepwise development
processes and procedures common to
the medications development paradigm,
i.e., a candidate compound must
successfully complete each necessary
pre-requisite step prior to being
advanced for further testing and
development. It is NIDA’s intention to
provide, assuming pre-requisite
preclinical and clinical safety,
preclinical and clinical trials services
sufficient to permit the completion of
Phase II hypothesis testing trials for
cocaine and methamphetamine
dependence indications. Assuming
demonstration and review of safety and
efficacy at the conclusion of Phase II
trials and subject to negotiation, NIDA
will consider undertaking Phase III
trials sufficient to permit Collaborator to
seek a U.S. New Drug Application
(NDA).
Please note that a CRADA is not a
funding mechanism. No NIH funding
may be provided to a Collaborator under
a CRADA. All assistance is provided
‘‘in-kind’’. Therefore the Collaborator
will bear the financial and
organizational costs of meeting its share
of obligations under any Research Plan
that may be negotiated in connection
with the CRADA.
‘‘Cooperative Research and
Development Agreement’’ or ‘‘CRADA’’
means the anticipated joint agreement to
be entered into by NIDA pursuant to the
Federal Technology Transfer Act of
1986 and Executive Order 12591 of
October 10, 1987 to collaborate on the
specific research project described
below.
The National Institute on Drug Abuse
seeks an agreement with a
pharmaceutical or biotechnology
company for joint research,
development, evaluation, and potential
commercialization of vigabatrin for the
treatment of cocaine and
methamphetamine dependence.
The CRADA aims include the rapid
publication of research results and the
timely exploitation of commercial
opportunities. The CRADA partner will
enjoy rights of first negotiation for
licensing Government rights to any
inventions arising under the agreement
and will advance funds payable upon
signing the CRADA to help defray
Government expenses for patenting
such inventions and other CRADArelated costs.
The expected duration of the CRADA
will be 3 to 5 years.
Selection criteria for choosing the
CRADA partner will include but not be
limited to:
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1. Ability to collaborate with NIDA on
further research and development of
this technology in Phase I and Phase II
clinical studies. All such studies will
occur in the United States and under
FDA IND rules. Demonstration of
experience and expertise in this or
related areas of technology and the
ability to provide intellectual
contribution to the ongoing research and
development. Ability to accomplish
objectives according to an appropriate
timetable to be outlined in the
Collaborator’s proposal. At an absolute
minimum, Collaborator must be able to
provide vigabatrin and placebo
sufficient to complete all clinical and
preclinical studies required in the
Research Plan.
2. Demonstration of the resources
(facilities, personnel and expertise)
necessary to perform research,
development and commercialization of
this technology.
3. Commitment of reasonable effort
and resources on research, development
and commercialization of this
technology.
4. Expertise in the commercial
development, production, marketing
and sales of products related to this area
of technology .
5. The level of financial support, if
any, the Collaborator will supply for
CRADA-related Government activities.
6. A willingness to cooperate with the
National Institute on Drug Abuse in the
publication of research results.
7. An agreement to be bound by the
DHHS rules involving human subjects,
patent rights and ethical treatment of
animals.
8. A willingness to accept the legal
provisions and language of the CRADA
with only minor modifications (if any).
9. Provisions for equitable
distribution of patent rights to any
inventions made during the course of
the subject CRADA research. Generally,
the rights of ownership are retained by
the organization which is the employer
of the inventor, with (1) an irrevocable,
nonexclusive, royalty-free license to the
Government (when a company
employee is the sole inventor) or (2) an
option to negotiate an exclusive or
nonexclusive license to the company on
terms that are appropriate (when a
Government employee is an inventor).
Dated: May 11, 2005.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 05–10066 Filed 5–19–05; 8:45 am]
BILLING CODE 4140–01–P
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, DHHS.
ACTION: Notice.
AGENCY:
SUMMARY: The inventions listed below
are owned by an agency of the U.S.
Government and are available for
licensing in the U.S. in accordance with
35 U.S.C. 207 to achieve expeditious
commercialization of results of
federally-funded research and
development. Foreign patent
applications are filed on selected
inventions to extend market coverage
for companies and may also be available
for licensing.
ADDRESSES: Licensing information and
copies of the U.S. patent applications
listed below may be obtained by writing
to the indicated licensing contact at the
Office of Technology Transfer, National
Institutes of Health, 6011 Executive
Boulevard, Suite 325, Rockville,
Maryland 20852–3804; telephone: (301)
496–7057; fax: (301) 402–0220. A signed
Confidential Disclosure Agreement will
be required to receive copies of the
patent applications.
Synthesis of Phosphocholine Ester
Derivatives and Conjugates Thereof
Louis J. Rezanka (NIA), U.S. Provisional
Application No. 60/623,762 filed 29
Oct 2004 (DHHS Reference No. E–
330–2004/0–US–01)
Licensing Contact: Michael
Shmilovich; (301) 435–5019;
shmilovm@mail.nih.gov.
Available for licensing and
commercial development is a method of
synthesizing EPC (4-Nitrophenyl-6-(Ophosphocholine) hydroxyhexanoate)
and methods of synthesizing
phosphocholine analogues and the
phosphocholine conjugates formed
therefrom. These molecules have
clinical and research applications as
anti-microbial agents. Specifically, EPC
conjugated to protein carriers has been
demonstrated to generate a protective
immune response to Streptococcus
pneumoniae. The invention provides a
process for EPC synthesis as well as for
its reaction intermediates for use in
synthesis.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
E:\FR\FM\20MYN1.SGM
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]]>Agencies
[Federal Register Volume 70, Number 97 (Friday, May 20, 2005)]
[Notices]
[Pages 29330-29332]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-10066]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Opportunity for a Cooperative Research and Development Agreement
(CRADA) for Research and Development of Vigabatrin as a Potential
Pharmacotherapy for the Treatment of Cocaine and Methamphetamine
Dependence
AGENCY: National Institutes of Health, PHS, DHHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The National Institute on Drug Abuse, a component of the
National Institutes of Health, Department of Health and Human Services
(DHHS) seeks an agreement with a pharmaceutical or biotechnology
company to test the hypotheses that vigabatrin may be a safe and
effective medication for the treatment of cocaine and methamphetamine
dependence.
A body of literature relevant to preclinical studies of vigabatrin
as a potential treatment agent for various types of substance
dependence (including cocaine and methamphetamine) and a more limited
body of literature concerning clinical results exists. As there are
currently no medications approved by the U. S. Food and Drug
Administration (FDA) for the treatment of cocaine and/or
methamphetamine dependence, and cocaine and methamphetamine dependence
have substantial negative public health impacts, the National Institute
on Drug Abuse is interested in evaluating the safety and efficacy of
vigabatrin for the treatment of cocaine and methamphetamine dependence.
[[Page 29331]]
Rationale for Studying Vigabatrin in Stimulant(s) Dependence
The dependence-producing properties of stimulants have been
associated with their pharmacological actions on the mesolimbic
dopamine reward pathways in the central nervous system (CNS). Gamma-
amino butyric acid (GABA) inhibits striatal dopamine release, and
attenuates cocaine-induced increases in extracellular dopamine in the
striatum and nucleus accumbens (Molina et. al., 1999). Selective
increases in GABAergic tone attenuate cocaine-induced dopamine release
without the apparent side effects typically associated with GABA
agonists. Therefore, targeting brain GABAergic systems is a potentially
effective pharmacologic treatment strategy for cocaine and
methamphetamine dependence (Molina et. al., 1999). Data from proof of
concept clinical trials of similar GABAergic medications e.g.
topiramate, baclofen, and tiagabine show efficacy in reducing cocaine
use or in preventing relapse to use. These data suggest that
vigabatrin, which possesses more potent GABAergic action, may be more
efficacious than these medications. Preclinical studies in animal
models have confirmed that dosing with vigabatrin can block the
manifestations of consumption of cocaine typically seen in these models
(Stromberg et. al., 2001), without impairing the usual dopamine
mechanisms necessary to maintain a stable equilibrium. In rodent
models, vigabatrin has been shown to reduce self-administration of
cocaine and alcohol (Stromberg et. al., 2001; Kushner et al., 1999),
and to block conditioned place preference induced by cocaine (Dewey et.
al, 1998), nicotine (Dewey et. al., 1999), and heroin (Paul, et. al.,
2001). Further, vigabatrin can reduce the increases in nucleus
accumbens dopamine induced by cocaine (Schiffer et. al., 2003), as well
as methamphetamine, heroin, and ethanol (Gerasimov et. al., 1999).
Vigabatrin (GVG) is an irreversible gamma-amino butyric acid (GABA)
transaminase inhibitor that produces a two to three fold rise in brain
GABA concentrations (Guberman et. al., 2000). Following oral
administration, vigabatrin readily crosses the blood-brain barrier and
is active within the central nervous system. It has been shown to be
effective, both as an add-on agent and in monotherapy in resistant and
newly-diagnosed epilepsy (Guberman et. al., 2000) and as first line
monotherapy in the treatment of infantile spasms (West syndrome)
(Hancock et. al., 1999). After oral dosing, vigabatrin is well absorbed
(bioavailability c. 75%) and widely distributed. The drug is eliminated
primarily by the renal route and is not significantly bound to plasma
proteins. The elimination half-life is approximately 5-9 hours in
healthy subjects and may be prolonged in elderly patients or those with
impaired renal function (Rey et. al., 1992). The usual adult dose of
vigabatrin for epilepsy is 1-3 g/day. There is no evidence that plasma
concentrations of vigabatrin correlate closely with therapeutic effects
(Brodie et. al., 2003).
There are anecdotal reports that dosing with vigabatrin prevents
the ``high'' associated with cocaine intake in humans dependent on
cocaine and can, therefore, result in decreased cocaine consumption.
Two open label pilot studies suggest a therapeutic effect in most
patients recruited in abstaining from cocaine or methamphetamine
(Brodie et. al., 2005) use (Brodie et. al., 2003; Brodie et. al.,
2005).
Therefore, it may be predicted that dosing with vigabatrin in a
cocaine dependent population might prevent the cocaine ``high'' and the
subsequent ``craving'', and possibly reduce the perceived need for
repeated use, and often higher, drug doses (Dewey et. al., 1999).
As an initial step in the clinical development of vigabatrin for
stimulants dependence, it is important to assess the potential efficacy
and safety of this compound in cocaine and methamphetamine dependent
subjects.
References
Brodie JD, Figueroa E, Dewey SL (2003). Treating cocaine addiction:
From preclinical to clinical experience with gamma-vinyl GABA.
Synapse 50: 261-265.
Brodie JD, Figueroa E, Lasha EM, Dewey SL (2005). Safety and
efficacy of gamma-vinyl GABA (GVG) for the treatment of
methamphetamine and cocaine addiction. Synapse 55(2): 122-125.
Dewey SL, Brodie JD, Gerasimov M, Horan B, Gardner EL, Ashby CR
(1999). A pharmacological strategy for the treatment of nicotine
addiction. Synapse 31: 76-86.
Dewey SL, Morgan SE, Ashby CR, Horan B, Gardner EL, Brodie JD
(1998). A novel strategy for the treatment of cocaine addiction.
Synapse 30: 119-129.
Gerasimov MR, Ashby CR, Gardner EL, Mills MJ, Brodie JD, Dewey SL
(1999). Gamma-Vinyl GABA inhibits methamphetamine, heroin, or
ethanol-induced increases in nucleus accumbens dopamine. Synapse 34:
11-19.
Gillis MC (2005). CPS: Compendium of Pharmaceutical and Specialties
(CPS). 37th Edition, Canadian Pharmaceutical Association, Ottawa,
pp: 1513-1515.
Guberman A, Bruni J & The Canadian Vigabatrin Study Group (2000).
Long-term open multicentre, add-on trial of vigabatrin in adult
resistant partial epilepsy. Seizure 9:112-118.
Hancock E, Osborne JP (1999). Vigabatrin in the treatment of
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DATES: NIDA will consider all proposals received within 45 days of the
date of publication of this notice. This notice is active until July 5,
2005.
ADDRESSES: Proposals and questions about this opportunity may be
addressed to Frank Vocci, Ph.D., Division of Pharmacotherapy and
Medical Consequences of Drug Abuse, National Institute on Drug Abuse,
6001 Executive Blvd., MSC 9551, Bethesda, Maryland 20892-9551. For
overnight mail service, 6001 Executive Blvd., Room 4123, Rockville,
Maryland 20852. Tel: (301) 443-2711, Fax: (301) 443-2599.
SUPPLEMENTARY INFORMATION: NIDA will consider proposals from all
qualified entities and will, subject to negotiation of the details of a
mutually agreed upon Research Plan, provide the CRADA Collaborator
access to its comprehensive preclinical and clinical trials resources
with the understanding that the CRADA Collaborator will be able to
utilize data derived from the CRADA to pursue regulatory filings in the
U.S. and abroad. NIDA's Medications Development Program possesses the
capacity to perform chemical synthesis, dosage form development,
pharmacokinetics, pharmacodynamics, toxicology, regulatory management,
and clinical testing (Phase I through Phase III) meeting FDA
requirements for Good Manufacturing, Good Laboratory Procedures, and
Good Clinical Practices standards. NIDA may apply these capacities in
the assessment of vigabatrin, as may be warranted based
[[Page 29332]]
on NIDA's evaluation of the information, capacities, and plans provided
by potential Collaborator(s).
NIDA follows stepwise development processes and procedures common
to the medications development paradigm, i.e., a candidate compound
must successfully complete each necessary pre-requisite step prior to
being advanced for further testing and development. It is NIDA's
intention to provide, assuming pre-requisite preclinical and clinical
safety, preclinical and clinical trials services sufficient to permit
the completion of Phase II hypothesis testing trials for cocaine and
methamphetamine dependence indications. Assuming demonstration and
review of safety and efficacy at the conclusion of Phase II trials and
subject to negotiation, NIDA will consider undertaking Phase III trials
sufficient to permit Collaborator to seek a U.S. New Drug Application
(NDA).
Please note that a CRADA is not a funding mechanism. No NIH funding
may be provided to a Collaborator under a CRADA. All assistance is
provided ``in-kind''. Therefore the Collaborator will bear the
financial and organizational costs of meeting its share of obligations
under any Research Plan that may be negotiated in connection with the
CRADA.
``Cooperative Research and Development Agreement'' or ``CRADA''
means the anticipated joint agreement to be entered into by NIDA
pursuant to the Federal Technology Transfer Act of 1986 and Executive
Order 12591 of October 10, 1987 to collaborate on the specific research
project described below.
The National Institute on Drug Abuse seeks an agreement with a
pharmaceutical or biotechnology company for joint research,
development, evaluation, and potential commercialization of vigabatrin
for the treatment of cocaine and methamphetamine dependence.
The CRADA aims include the rapid publication of research results
and the timely exploitation of commercial opportunities. The CRADA
partner will enjoy rights of first negotiation for licensing Government
rights to any inventions arising under the agreement and will advance
funds payable upon signing the CRADA to help defray Government expenses
for patenting such inventions and other CRADA-related costs.
The expected duration of the CRADA will be 3 to 5 years.
Selection criteria for choosing the CRADA partner will include but
not be limited to:
1. Ability to collaborate with NIDA on further research and
development of this technology in Phase I and Phase II clinical
studies. All such studies will occur in the United States and under FDA
IND rules. Demonstration of experience and expertise in this or related
areas of technology and the ability to provide intellectual
contribution to the ongoing research and development. Ability to
accomplish objectives according to an appropriate timetable to be
outlined in the Collaborator's proposal. At an absolute minimum,
Collaborator must be able to provide vigabatrin and placebo sufficient
to complete all clinical and preclinical studies required in the
Research Plan.
2. Demonstration of the resources (facilities, personnel and
expertise) necessary to perform research, development and
commercialization of this technology.
3. Commitment of reasonable effort and resources on research,
development and commercialization of this technology.
4. Expertise in the commercial development, production, marketing
and sales of products related to this area of technology .
5. The level of financial support, if any, the Collaborator will
supply for CRADA-related Government activities.
6. A willingness to cooperate with the National Institute on Drug
Abuse in the publication of research results.
7. An agreement to be bound by the DHHS rules involving human
subjects, patent rights and ethical treatment of animals.
8. A willingness to accept the legal provisions and language of the
CRADA with only minor modifications (if any).
9. Provisions for equitable distribution of patent rights to any
inventions made during the course of the subject CRADA research.
Generally, the rights of ownership are retained by the organization
which is the employer of the inventor, with (1) an irrevocable,
nonexclusive, royalty-free license to the Government (when a company
employee is the sole inventor) or (2) an option to negotiate an
exclusive or nonexclusive license to the company on terms that are
appropriate (when a Government employee is an inventor).
Dated: May 11, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 05-10066 Filed 5-19-05; 8:45 am]
BILLING CODE 4140-01-P
